Introduction to Contrast-Enhanced Imaging

Contrast-enhanced imaging combines into a powerful diagnostic tool all the diagnostic insight provided by standard anatomical imaging along with the interpretation of the transport kinetics of detectable tracers, referred to as “contrast agents.” These are substances that comply with all the safety requirements to be injected into the bloodstream and subsequently detected by dedicated sensors. Contrast-enhanced imaging is a powerful diagnostic tool combining all the diagnostic insight provided by standard anatomical imaging along with the interpretation of the transport kinetics of detectable tracers, referred to as “contrast agents.” These are substances that comply with all the safety requirements to be injected into the bloodstream and subsequently detected by dedicated sensors. Originally, the detection of an injected tracer required physical contact with a sensor, usually positioned on a catheter tip. A typical example is provided by thermodilution measurements, making use of a thermistor [1, 2]. An alternative option consisted of drawing blood and performing the sensing outside the body. An example is provided by lithium dilution systems [3]. By any of these solutions, the tracer concentration can be sampled at few locations only, depending on the number of adopted catheters. Moreover, the invasiveness of these methods represents an important limiting factor, excluding the use of dilution principles in outpatients, outside the intensive care unit or operating theater. The possibility of detecting tracers without contact, but just using imaging technology, has opened up new immense possibilities for the diagnostic use of contrast agents. When the concentration of these agents can be measured in space and time, it provides valuable inputs for the identification of pharmacokinetic models enabling the assessment of physiological and functional parameters of diagnostic relevance. Obviously, this requires coping with complex, technical problems, ranging from the calibration of the imaging system and its ability to provide an accurate estimation of the contrast-agent concentration, up to the spatiotemporal resolution of the imaging system and the identifiability of the proposed pharmacokinetic models. These complex problems have different solutions depending on the adopted imaging technology and contrast agent, which rely on different physical principles for detection and quantification. Before discussing use and quantification of contrast agents, in this chapter we first provide a brief survey of the adopted imaging technology: magnetic resonance imaging (MRI), ultrasound (US), X-ray computed tomography (CT), and nuclear scintigraphy. This provides the technological basis for contrast-enhanced imaging. While MRI, US, and X-ray imaging do not require the use of contrast agents to produce diagnostic images, nuclear imaging, referred to as scintigraphy, generates images by detection of the radiation released by decaying radioisotopes, which must be injected in the bloodstream. Because of this, scintigraphy represents historically the first imaging technology integrating imaging with contrast enhancement and pharmacokinetic modeling. At the end of this chapter, the use of contrast enhancement by the other imaging technologies will also be introduced, along with its clinical implication and perspectives. Being injected in the body, contrast agents have strict requirements not only in terms of detectability, but especially in terms of safety. These will be briefly discussed in Sect. 1.2 along with the growing market share of contrast-enhanced imaging, motivated by the additional diagnostic possibilities provided by contrast-enhanced functional imaging.